Author: David E. Gordon; Gwendolyn M. Jang; Mehdi Bouhaddou; Jiewei Xu; Kirsten Obernier; Matthew J O'Meara; Jeffrey Z. Guo; Danielle L. Swaney; Tia A. Tummino; Ruth Huttenhain; Robyn Kaake; Alicia L. Richards; Beril Tutuncuoglu; Helene Foussard; Jyoti Batra; Kelsey Haas; Maya Modak; Minkyu Kim; Paige Haas; Benjamin J. Polacco; Hannes Braberg; Jacqueline M. Fabius; Manon Eckhardt; Margaret Soucheray; Melanie Brewer; Merve Cakir; Michael J. McGregor; Qiongyu Li; Zun Zar Chi Naing; Yuan Zhou; Shiming Peng; Ilsa T. Kirby; James E. Melnyk; John S Chorba; Kevin Lou; Shizhong A. Dai; Wenqi Shen; Ying Shi; Ziyang Zhang; Inigo Barrio-Hernandez; Danish Memon; Claudia Hernandez-Armenta; Christopher J.P. Mathy; Tina Perica; Kala B. Pilla; Sai J. Ganesan; Daniel J. Saltzberg; Rakesh Ramachandran; Xi Liu; Sara B. Rosenthal; Lorenzo Calviello; Srivats Venkataramanan; Yizhu Lin; Stephanie A. Wankowicz; Markus Bohn; Phillip P. Sharp; Raphael Trenker; Janet M. Young; Devin A. Cavero; Joseph Hiatt; Theo Roth; Ujjwal Rathore; Advait Subramanian; Julia Noack; Mathieu Hubert; Ferdinand Roesch; Thomas Vallet; Björn Meyer; Kris M. White; Lisa Miorin; Oren S. Rosenberg; Kliment A. Verba; David Agard; Melanie Ott; Michael Emerman; Davide Ruggero; Adolfo Garcí-Sastre; Natalia Jura; Mark von Zastrow; Jack Taunton; Olivier Schwartz; Marco Vignuzzi; Christophe d'Enfert; Shaeri Mukherjee; Matt Jacobson; Harmit S. Malik; Danica G Fujimori; Trey Ideker; Charles S Craik; Stephen Floor; James S. Fraser; John Gross; Andrej Sali; Tanja Kortemme; Pedro Beltrao; Kevan Shokat; Brian K. Shoichet; Nevan J. Krogan
Title: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Document date: 2020_3_22
ID: 38d6gb7o_24
Snippet: Beyond direct interactions, several drug-pathway interactions seemed noteworthy. The human purine biosynthesis enzyme Inosine-5′-monophosphate dehydrogenase (IMPDH2) interacts with the viral protein nsp14. Several chemically diverse compounds inhibit IMPDH2, including the clinically approved mycophenolic acid (20 nM), the approved antiviral drug ribavirin (200 nM), and the investigational new drug Merimepodib (10 nM) (Table 1a) . Intriguingly,.....
Document: Beyond direct interactions, several drug-pathway interactions seemed noteworthy. The human purine biosynthesis enzyme Inosine-5′-monophosphate dehydrogenase (IMPDH2) interacts with the viral protein nsp14. Several chemically diverse compounds inhibit IMPDH2, including the clinically approved mycophenolic acid (20 nM), the approved antiviral drug ribavirin (200 nM), and the investigational new drug Merimepodib (10 nM) (Table 1a) . Intriguingly, the preclinical molecule Sanglifehrin A (Table 1b) is known to act as a molecular glue linking IMPDH with cyclophilin A (Fig. 5b) 73 , which itself is implicated in viral capsid packaging, even though it itself is not a human "prey" in the viral-human protein interactome. Similarly, direct viral-human interactions with proteins regulated by the mTORC1 pathway, such as LARP1, and FKBP7, which interact with the viral N and Orf8 proteins, led us to inhibitors of mTORC1, even though that kinase itself is not found to directly interact with a viral protein (Fig. 5c ). Sapanisertib and rapamycin are low nM inhibitors of mTORC1, while metformin is an indirect modulator of this protein complex.
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